Degenerative Disorders Flashcards
1
Q
Donepezil
A
Centrally acting cholinesterase inhibitor
Alzheimers
2
Q
Rivastigmine
A
Centrally acting cholinesterase inhibitor
Alzheimers
3
Q
Galantamine
A
Centrally acting cholinesterase inhibitor
Alzheimers
4
Q
Memantine
A
NMDA Channel blocker
Slows disease progression in Alzheimer’s
5
Q
Levodopa
A
Restores DA levels in the basal ganglia by entering CNS via amino acid transporters. Decarboxylated to DA in cells expressing L-AAAD.
- 2% gets into the brain; co-administer with carbidopa=L-AAAD inhibitor that doesn’t cross BBB (Increases dose in CNS and peripheral side effects).
- Can also be co-administered with COMT inhibitor=entacapone.
- Very short half life; absorption depends on GI contents (amino acid transporters that are responsible for uptake can be saturated with high protein meal).
- Effectiveness lost after 1st few years of treatment
6
Q
Levodopa–side effects
A
- CNS side effects: aren’t alleviated by carbidopa. Dyskinesia, Dementia, confusion
- Peripheral side effects: reduced by carbidopa. Nausea, Postural hypotension, Arrhythmias, HTN
7
Q
Levodopa–drug interactions
A
- Pyridoxine; increases peripheral DA metabolism
- MAO inhibitors: HTN (except selegiline)
- Halothane: arrhythmia
- Antipsychotics that are DA Receptor antagonists
8
Q
Levodopa–containdications
A
- Glaucoma
- Psychosis
- Cardiac disease with arrhythmia
- Malignant melanoma
9
Q
DA Receptor Agonists
A
- Mimic dopamine without need for intact nerve terminals. Mechanism: DA receptor agonists in striatum.
- Advantages: Receptor subtype selectivity, longer T1/2, less DA-dependent oxidative stress?
- Firstline: longer duration, reduce DA synthesis so less oxidative toxicity. Initial therapy in young patients.
10
Q
Pramipexole and Ropinerole
A
D2 Receptor Agonists
Most commonly used
11
Q
Apomorphine
A
- High affinity D4 agonist; moderate for D2/3/5
- Subcutaneous injection for immediate therapy of an “off” episode
- Reserved for patients who are refractory to other treatments
- Side effects: Increased QT prolongation and injection site reaction
12
Q
DA Receptor Agonists Side Effects
A
- Nausea
- Fatigue
- Daytime sleepiness
- CNS toxicity: confusion (worse than L-Dopa), dyskinesia (better than with L-Dopa)
13
Q
MAO Inhibitors
A
- Need to be careful…in liver, MAO-A metabolizes tyramine, which is a sympathomimetic.
- MAO-B=major form in the brain
- MAO inhibition prolonges action of dopamine and reduces oxidative stress on neurons
- Mechanism: selective, irreversible inhibition of MAO-B.
14
Q
Selegiline and Rasagiline
A
- MAO-B inhibitors
- Prescribed as soon as disease is diagnosed; benefit is modest
- advanced disease: combined with L-Dopa to prolong its half life
- Anti-depressant
- Side effects: can worsen side effects of L-dopa, and is metabolized to amphetamine/methamphetamine–causes anxiety and insomnia.
- When administered with TCAs or SSRIs can lead to Serotonin Syndrome (stupor, rigidity, agitation, hyperthermia)
15
Q
Tolcapone, Entacapone
A
- COMT metabolizes DA; inhibition prolongs DA action and decreases L-Dopa metabolism to non-DA metabolites
- Tolcapone: long T1/2 and inhibits both peripheral and central COMT
- Entacapone: short T1/2 and does not penetrate CNS well; usually co-administered with L-Dopa to eliminate peripheral metabolism.
- Side Effects: nausea, orthostatic hypotension, vivid dreams, confusion, hallucinations
- Tolcapone can cause liver toxicity–not used except as last resort
16
Q
Trihexyphenidyl and Benztropine
A
- Antagonists of striatal muscarinic receptors; blunt overactivity of cholinergic interneurons in striatum that are uninhibited by loss of dopamine.
- Modest efficiacy; not good against bradykinesia
- 3rd choice after L-dopa and DA agonists
- Side effects: sedation, mental confusion, voiding etc. (like atropine).
17
Q
Amantadine
A
- Anti viral; increases DA release, mildly anticholinergic, NMDA receptor blocker
- Less effective…given with L-Dopa or anticholinergics
- only useful if L-Dopa also is effective
- Side effects: dizziness, lethargy, sleep disturbance, peripheral edema
- Contraindicated with CHF
18
Q
Riluzole
A
- Inhibits NMDA channels and glutamater release; increases uptake
- modest but genuine effects on ALS
- increases lifespan 2-3 months
